Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial)

Cancers
Ivana Bratic HenchSwiss Group For Clinical Cancer Research Sakk

Abstract

Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies. However, a robust test for the assessment of the ARV7 status in patient samples is still missing. Here, we implemented an RT-qPCR-based assay for detection of AR full length (ARFL)/ARV7 expression in CTCs for clinical use. Additionally, as a proof-of-principle, we validated a cohort of 95 mCRPC patients initiating first line treatment with enzalutamide or enzalutamide/metformin within a clinical trial. A total of 95 mCRPC patients were analyzed at baseline of whom 27.3% (26/95) had ARFL+ARV7+, 23.1% (22/95) had ARFL+ARV7-, 23.1% (22/95) had ARFL-ARV7-, and 1.1% (1/95) had ARFL-ARV7+ CTCs. In 11.6% (11/95), no CTCs could be isolated. A total of 25/95 patients had another CTC analysis at p...Continue Reading

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Citations

Jul 20, 2020·International Journal of Cancer. Journal International Du Cancer·Isabel HeidrichKlaus Pantel
Jul 18, 2020·Current Opinion in Oncology·Lisanne F van DesselMartijn P Lolkema
Nov 26, 2020·Pathology·Tatjana Vlajnic, Lukas Bubendorf
Jan 22, 2021·Biochemical and Biophysical Research Communications·Hongwen CaoYigeng Feng

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Methods Mentioned

BETA
biopsies
PCR
blood draw
Chip

Clinical Trials Mentioned

NCT02640534

Software Mentioned

Adna Detect
AdnaTest
Adna

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